The discussion of any work, publications, sales, or activity anywhere in this submission, including in any documents submitted with this application, shall not be taken as an admission that any such work constitutes prior art. The discussion of any activity, work, or publication herein is not an admission that such activity, work, or publication existed or was known in any particular jurisdiction.
A minimally invasive method for sampling biological fluids is a prerequisite to performing either periodic or continuous monitoring of physiological systems. Furthermore, minimally invasive methods of delivering drugs or other substances, painlessly and optionally continuously and optionally in combination with monitoring, a timer, or other means for automatically determining when to administer the substance, would be useful in many treatment applications. In particular, blood and cellular interstitial fluid (ISF) contain important metabolic and immunological biomolecules whose time varying concentrations are important indicators of various states of health and disease. The transdermal sampling of small volumes of blood for glucose concentration measurement is part of the daily routine for many diabetic patients to monitor and control the symptoms of their disease. Although they are considered minimally invasive techniques, needle pricks and lancets do produce tissue damage and patient discomfort. The use of microtechnology to reduce the size of needles to minimize discomfort is a rapidly developing arena of investigation for the transcutaneous delivery of drugs.
The epidermis forms the outermost skin barrier. It is relatively impermeable to both polar and non-polar lipophilic molecules. Its outermost layer, the stratum corneum, varies in thickness from 10-40 microns and consists of adherent dead cells, with thickened, cross-linked sub-plasma membrane protein “envelopes” encased in pericellular lipids. The epidermis, which varies in thickness from 50-100 microns, sits atop the lower layer of the skin, the dermis, from which it is separated by a proteinaceous basement membrane. Blood vessels and capillaries lie in the dermis. The epidermis is devoid of blood vessels and receives its nourishment by diffusion from the capillaries that lie in the superficial dermis directly beneath the dermo-epidermal junction. It is this area that is optimally targeted for ISF extraction-superficial enough to be painless, yet in close proximity to capillary blood flow for monitoring equilibrating constituents of interest (e.g. glucose).
Despite recent advances in the configuration and/or fabrication of semiconductor-based or other microneedles, there still exits a need for improved needle designs.